Rescuing inflammatory microenvironment induced senescence via MgO immune mediated asymmetric short fibers for accelerating diabetic wound repair

Ongoing disturbance of the immune microenvironment under diabetes mellitus is a significant obstacle to optimal wound repair. Persistence of the local inflammatory niche from incomplete or dysregulated regression of acute inflammation causes the surrounding tissues to undergo immune-induced senescence. Inspired by the natural tissue structure of the extracellular matrix and metal immunotherapy, we developed an asymmetric short-fiber Gelatin/Poly(L-lactic acid) aerogel scaffold loaded with magnesium oxide nanoparticles (GP@MgO aerogel). This innovative short-fiber aerogel scaffold addresses the two-dimensional longitudinal collapse of electrospinning. It achieves a spatial three-dimensional bionic structure that provides additional cell adhesion sites and slowly absorbs tissue exudates. The gravity-induced short fibers form asymmetric densities at both ends, facilitating exudate management. Meanwhile, this aerogel relieves over-activated inflammation and alleviates defects in the cellular energy supply, accelerating neovascularization and reducing the aging process of tissues adjacent to the trauma. Furthermore, GP@MgO modulates macrophage polarization and decreases the release of senescence-associated secretory phenotypes, achieving accelerated revascularization and re-epithelialization in a full-thickness skin model of diabetic rats. In conclusion, these findings indicate that short-fiber GP@MgO aerogels offer a measure to regulate biochemical functions and physiological responses for the rapid closure of diabetic wounds through metal immunotherapy.